COMET: Communication-optimised multi-threaded error-detection technique

© 2016 ACM. Relentless technology scaling has made transistors more vulnerable to soft, or transient, errors. To keep systems robust against these, current error detection techniques use different types of redundancy at the hardware or the software level. A consequence of these additional protection mechanisms is that these systems tend to become slower. In particular, software error-detection techniques degrade performance considerably, limiting their uptake. This paper focuses on software redundant multi-threading error detection, a compiler-based technique that makes use of redundant cores within a multi-core system to perform error checking. Implementations of this scheme feature two threads that execute almost the same code: the main thread runs the original code and the checker thread executes code to verify the correctness of the original. The main thread communicates the values that require checking to the checker thread to use in its comparisons. We identify a major performance bottleneck in existing schemes: poorly performing inter-core communication and the generated code associated with it. Our study shows this is a major performance impediment within existing techniques since the two threads require extremely fine-grained communication, on the order of every few instructions. We alleviate this bottleneck with a series of code generation optimisations at the compiler level. We propose COMET (Communication-Optimised Multi-threaded Error-detection Technique), which improves performance across the NAS parallel benchmarks by 31.4% (on average) compared to the state-of-the-art, without affecting fault-coverage

Lynx: Using OS and hardware support for fast fine-grained inter-core communication

Designing high-performance software queues for fast intercore communication is challenging, but critical for maximising software parallelism. State-of-the-art single-producer / single-consumer queues for streaming applications contain multiple sections, requiring the producer and consumer to operate independently on different sections from each other. While these queues perform well for coarse-grained data transfers, they perform poorly in the fine-grained case. This paper proposes Lynx, a novel SP/SC queue, specifically tuned for fine-grained communication. Lynx is built from the ground up, reducing the generated code on the critical-path to just two operations per enqueue and dequeue. To achieve this it relies on existing commodity processor hardware and operating system exception handling support to deal with infrequent queue maintenance operations. Lynx outperforms the state-of-the art by up to 1.57× in total 64-bit throughput reaching a peak throughput of 15.7GB/s on a common desktop system. Real applications using Lynx get a performance improvement of up to 1.4×.This work was supported by the Engineering and Physical Sciences Research Council (EPSRC), through grant reference EP/K026399/1.This is the author accepted manuscript. The final version is available from Association for Computing Machinery via http://dx.doi.org/10.1145/2925426.2926274

Development and Psychometric Evaluation of the Questionnaire of Ethical Leadership (QueL)

In this five-study paper, we developed and validated the Questionnaire of ethical Leadership (QueL). We examined the factor structure of QueL using Exploratory and Confirmatory Factor Analysis, along with measurement invariance techniques, using data from more than 1,200 leaders and subordinates working in Greece. Exploratory analysis indicated two latent highly-correlated factors that were labeled “Telos” and “Ethos.” Confirmatory analysis verified a bifactor solution. The bifactor QueL showed configural, metric, and scalar invariance across independent samples of leaders and subordinates. QueL was found to be a reliable measure across time and occupational groups (leaders and subordinates). We found criterion correlations in the expected direction with other ethical leadership scales, related constructs (i.e., integrity, trust, ethical climate), as well as workplace attitudes and behaviors (i.e., burnout, organizational commitment, organizational citizenship behaviors, deviant behaviors), leadership characteristics (transformational and transactional leadership, abusive supervision, personality), and socio-demographics (i.e., educational level and gender). We conclude that the new measure is a valuable tool for measuring workplace ethical leadership

Exercise tolerance and quality of life in patients with known or suspected coronary artery disease

Background: Coronary artery disease (CAD) is known to impact on patients’ physical and mental health. The relationship between performance on treadmill exercise tolerance test (ETT) and health-related quality of life (HRQL)has never been specifically investigated in the setting of CAD. Methods: Consecutive patients undergoing an ETT with the Bruce protocol during a diagnostic workup for CAD (n = 1,631, age 55 ± 12 years) were evaluated. Exercise-related indices were recorded. Detailed information on cardiovascular risk factors and past medical history were obtained. HRQLwas assessed with the use of the validated 36-Item Short Form Survey (SF-36) questionnaire. Results: Increasing age and the presence of cardiovascular risk factors and comorbidities correlated with lower scores on the physical and mental health component of SF-36(all P < 0.05). Subjects with arrhythmias during exercise and slow recovery of systolic blood pressure had lower scores on the physical health indices or the Social Role Functioning component (P < 0.05). Achieved target heart rate and good exercise tolerance were independently associated with better scores of the physical and mental health domains of SF-36 and overall HRQLscores (β = 0.05 for target HR and PCS-36, β = 1.86 and β = 1.66 per increasing stage of exercise tolerance and PCS-36 and MCS-36, respectively, P < 0.001 for all associations). Ischemic ECG changes were associated with worse scores on Physical Functioning (β = − 3.2, P = 0.02) and Bodily Pain (β = − 4.55, P = 0.026). Conclusion: ETT parameters are associated with HRQL indices in patients evaluated for possible CAD. Physical conditioning may increase patient well-being and could serve as a complementary target in conjunction with cardiovascular drug therapy

Economic evaluation of pharmacogenomic-guided antiplatelet treatment in Spanish patients suffering from acute coronary syndrome participating in the U-PGx PREPARE study

BackgroundCardiovascular diseases and especially Acute Coronary Syndrome (ACS) constitute a major health issue impacting millions of patients worldwide. Being a leading cause of death and hospital admissions in many European countries including Spain, it accounts for enormous amounts of healthcare expenditures for its management. Clopidogrel is one of the oldest antiplatelet medications used as standard of care in ACS.MethodsIn this study, we performed an economic evaluation study to estimate whether a genome-guided clopidogrel treatment is cost-effective compared to conventional one in a large cohort of 243 individuals of Spanish origin suffering from ACS and treated with clopidogrel. Data were derived from the U-PGx PREPARE clinical trial. Effectiveness was measured as survival of individuals while study data on safety and efficacy, as well as on resource utilization associated with each adverse drug reaction were used to measure costs to treat these adverse drug reactions. A generalized linear regression model was used to estimate cost differences for both study groups.ResultsBased on our findings, PGx-guided treatment group is cost-effective. PGx-guided treatment demonstrated to have 50% less hospital admissions, reduced emergency visits and almost 13% less ADRs compared to the non-PGx approach with mean QALY 1.07 (95% CI, 1.04-1.10) versus 1.06 (95% CI, 1.03-1.09) for the control group, while life years for both groups were 1.24 (95% CI, 1.20-1.26) and 1.23 (95% CI, 1.19-1.26), respectively. The mean total cost of PGx-guided treatment was 50% less expensive than conventional therapy with clopidogrel [euro883 (95% UI, euro316-euro1582), compared to euro1,755 (95% UI, euro765-euro2949)].ConclusionThese findings suggest that PGx-guided clopidogrel treatment represents a cost-effective option for patients suffering from ACS in the Spanish healthcare setting.Personalised Therapeutic

Correction: A european spectrum of pharmacogenomic biomarkers: Implications for clinical pharmacogenomics (PLoS ONE (2016) 11:9 (e0162866) DOI: 10.1371/journal.pone.0162866)

The thirty-Third author's name is spelled incorrectly. The correct name is: Jadranka Sertić

A European spectrum of pharmacogenomic biomarkers: Implications for clinical pharmacogenomics

Pharmacogenomics aims to correlate inter-individual differences of drug efficacy and/or toxicity with the underlying genetic composition, particularly in genes encoding for protein factors and enzymes involved in drug metabolism and transport. In several European populations, particularly in countries with lower income, information related to the prevalence of pharmacogenomic biomarkers is incomplete or lacking. Here, we have implemented the microattribution approach to assess the pharmacogenomic biomarkers allelic spectrum in 18 European populations, mostly from developing European countries, by analyzing 1,931 pharmacogenomics biomarkers in 231 genes. Our data show significant interpopulation pharmacogenomic biomarker allele frequency differences, particularly in 7 clinically actionable pharmacogenomic biomarkers in 7 European populations, affecting drug efficacy and/or toxicity of 51 medication treatment modalities. These data also reflect on the differences observed in the prevalence of high-risk genotypes in these populations, as far as common markers in the CYP2C9, CYP2C19, CYP3A5, VKORC1, SLCO1B1 and TPMT pharmacogenes are concerned. Also, our data demonstrate notable differences in predicted genotype-based warfarin dosing among these populations. Our findings can be exploited not only to develop guidelines for medical prioritization, but most importantly to facilitate integration of pharmacogenomics and to support pre-emptive pharmacogenomic testing. This may subsequently contribute towards significant cost-savings in the overall healthcare expenditure in the participating countries, where pharmacogenomics implementation proves to be cost-effective

Keratan sulphate in the tumour environment

Keratan sulphate (KS) is a bioactive glycosaminoglycan (GAG) of some complexity composed of the repeat disaccharide D-galactose β1→4 glycosidically linked to N-acetyl glucosamine. During the biosynthesis of KS, a family of glycosyltransferase and sulphotransferase enzymes act sequentially and in a coordinated fashion to add D-galactose (D-Gal) then N-acetyl glucosamine (GlcNAc) to a GlcNAc acceptor residue at the reducing terminus of a nascent KS chain to effect chain elongation. D-Gal and GlcNAc can both undergo sulphation at C6 but this occurs more frequently on GlcNAc than D-Gal. Sulphation along the developing KS chain is not uniform and contains regions of variable length where no sulphation occurs, regions which are monosulphated mainly on GlcNAc and further regions of high sulphation where both of the repeat disaccharides are sulphated. Each of these respective regions in the KS chain can be of variable length leading to KS complexity in terms of chain length and charge localization along the KS chain. Like other GAGs, it is these variably sulphated regions in KS which define its interactive properties with ligands such as growth factors, morphogens and cytokines and which determine the functional properties of tissues containing KS. Further adding to KS complexity is the identification of three different linkage structures in KS to asparagine (N-linked) or to threonine or serine residues (O-linked) in proteoglycan core proteins which has allowed the categorization of KS into three types, namely KS-I (corneal KS, N-linked), KS-II (skeletal KS, O-linked) or KS-III (brain KS, O-linked). KS-I to -III are also subject to variable addition of L-fucose and sialic acid groups. Furthermore, the GlcNAc residues of some members of the mucin-like glycoprotein family can also act as acceptor molecules for the addition of D-Gal and GlcNAc residues which can also be sulphated leading to small low sulphation glycoforms of KS. These differ from the more heavily sulphated KS chains found on proteoglycans. Like other GAGs, KS has evolved molecular recognition and information transfer properties over hundreds of millions of years of vertebrate and invertebrate evolution which equips them with cell mediatory properties in normal cellular processes and in aberrant pathological situations such as in tumourogenesis. Two KS-proteoglycans in particular, podocalyxin and lumican, are cell membrane, intracellular or stromal tissue–associated components with roles in the promotion or regulation of tumour development, mucin-like KS glycoproteins may also contribute to tumourogenesis. A greater understanding of the biology of KS may allow better methodology to be developed to more effectively combat tumourogenic processes

COMET: Communication-optimised multi-threaded error-detection technique

© 2016 ACM. Relentless technology scaling has made transistors more vulnerable to soft, or transient, errors. To keep systems robust against these, current error detection techniques use different types of redundancy at the hardware or the software level. A consequence of these additional protection mechanisms is that these systems tend to become slower. In particular, software error-detection techniques degrade performance considerably, limiting their uptake. This paper focuses on software redundant multi-threading error detection, a compiler-based technique that makes use of redundant cores within a multi-core system to perform error checking. Implementations of this scheme feature two threads that execute almost the same code: the main thread runs the original code and the checker thread executes code to verify the correctness of the original. The main thread communicates the values that require checking to the checker thread to use in its comparisons. We identify a major performance bottleneck in existing schemes: poorly performing inter-core communication and the generated code associated with it. Our study shows this is a major performance impediment within existing techniques since the two threads require extremely fine-grained communication, on the order of every few instructions. We alleviate this bottleneck with a series of code generation optimisations at the compiler level. We propose COMET (Communication-Optimised Multi-threaded Error-detection Technique), which improves performance across the NAS parallel benchmarks by 31.4% (on average) compared to the state-of-the-art, without affecting fault-coverage

Από τον κύκλο στην έλλειψη, από τον Εύδοξο έως τον Κέπλερ

96 σ.Αναφέρω διάφορους αρχαίους αστρονόμους και φιλόσοφους από τον Εύδοξο έως τον Κέπλερ καθώς και τα γεωμετρικά μοντέλα τα οποία αυτοί εισήγαγαν για να ερμηνεύσουν τις περίπλοκες κινήσεις των ουρανίων σωμάτων.Περιγράφω πως από το γεωκεντρικό σύστημα και τις κυκλικές κινήσεις φτάσαμε στο ηλιοκεντρικό σύστημα και τις ελλειψοειδής κινήσεις.Ι cite various ancient astronomers and philosophers from Eudoxus to Kepler and the geometric models which they introduced to explain the complicated movements of celestial bodies. I describe how the geocentric system and circular motion evolved into the heliocentric system and elliptical motion.Μαρία Κ. Μητροπούλο